The reversal of adaptive changes induced in rats by meal-feeding was investigated. Increases in adipose tissue lipogenic enzymes and in vitro rates of fatty acid synthesis induced by meal-feeding slowly returned to values similar to those observed in nibbling rats over a 6- week period after the meal-fed rats were allowed to return to a nibbling regimen. During this 6-week period these converted animals gained more body fat than did the nibbling or meal-fed controls. Glucose tolerance tests were conducted in meal-fed and nibbling rats fed high carbohydrate or high fat diets. Rats fed the high-fat diets or high-carbohydrate diets containing sucrose exhibited an impaired glucose tolerance when compared with rats fed the high-carbohydrate glucose containing diet. Regardless of diet fed, meal-fed rats exhibited lower blood glucose levels following the glucose load than did nibbling rats. The time course of lipogenic enzyme activity and fatty acid synthesis changes in adipose tissue from rats being switched from meal-eating to nibbling suggested that changes in fatty acid synthesis preceded changes in fatty acid synthetase, citrate cleavage enzyme and malic enzyme activity.